Long-Term Follow-Up of High-Risk Breast Lesions at Vacuum-Assisted Biopsy without Subsequent Surgical Resection.

Introduction: B3-lesions of the breast are a heterogeneous group of neoplasms, associated with a higher risk of breast cancer. Recent studies show a low upgrade rate into malignancy after subsequent open surgical excision (OE) of most B3-lesions when proven by vacuum-assisted biopsy (VAB). However, there is a lack of long-term follow-up data after VAB of high-risk lesions. The primary aim of this study was to demonstrate whether follow-up of B3 lesions is a beneficial and reliable alternative to OE in terms of long-term outcome. The secondary aim was to identify patient and lesion characteristics of B3 lesions for which OE is still necessary. Methods: This retrospective multicenter study was conducted at 8 Swiss breast centers between 2010 and 2019. A total of 278 women (mean age: 53.5 ± 10.7 years) with 286 B3-lesions who had observation only and who had at least 24 months of follow-up were included. Any event during follow-up (ductal carcinoma in situ [DCIS], invasive cancer, new B3-lesion) was systematically recorded. Data from women who had an event during follow-up were compared with those who did not. The results for the different B3 lesions were analyzed using the t test and Fisher's exact test. A p value of <0.05 was considered statistically significant. Results: The median follow-up interval was 59 months (range: 24-143 months) with 52% (148/286) having a follow-up of more than 5 years. During follow-up, in 42 women, 44 suspicious lesions occurred, with 36.4% (16/44) being invasive cancer and 6.8% (3/44) being DCIS. Thus, 6.6% (19/286) of all women developed malignancy during follow-up after a median follow-up interval of 6.5 years (range: 31-119 months). The initial histology of the B3 lesion influenced the subsequent occurrence of a malignant lesion during follow-up (p < 0.038). The highest malignancy-developing rate was observed in atypical ductal hyperplasia (ADH) (24%, 19/79), while all other B3-lesions had malignant findings ipsi- and contralateral between 0% and 6%. The results were not influenced by the VAB method (Mx-, US-, magnetic resonance imaging-guided), the radiological characteristics of the lesion, or the age or menopausal status of the patient (p > 0.12). Conclusion: With a low risk of <6% of developing malignancy, VAB followed by long-term follow-up is a safe alternative to OE for most B3-lesions. A higher malignancy rate only occurred in ADH (24%). Based on our results, radiological follow-up should be bilateral, preferable using the technique of initial diagnosis. As we observed a late peak (6-7 years) of breast malignancies after B3-lesions, follow-up should be continued for a longer period (>10 years). Knowledge of these long-term outcome results will be helpful in making treatment decisions and determining the optimal radiological follow-up interval.

ICD-Based Cause of Death Statistics Fail to Provide Reliable Data for Medical Aid in Dying.

Objectives: To evaluate the most recent developments of medical aid in dying (MAID) in Switzerland and to test the reliability of reporting this phenomenon in cause of death statistics. Methods: By reviewing the MAID cases between 2018 and 2020, we compared the diseases and conditions underlying MAID reported by the ICD-based statistics provided by the Swiss Federal Statistical Office (FSO, n = 3,623) and those provided by the largest right-to-die organization EXIT (n = 2,680). Results: EXIT reported the motivations underlying the desire for death in a mixture of disease-specific and symptom-oriented categories; the latter including, for example, multimorbidity (26% of cases), and chronic pain (8%). Symptom-oriented categories were not included in the ICD-based FSO statistics. This led to the fact that the distribution of the diseases/conditions underlying MAID differed in 30%-40% of cases between both statistics. Conclusion: In order to reliably follow developments and trends in MAID, the diseases/conditions underlying the wish to die must be accurately recorded. Current methods of data collection using the ICD classification do not capture this information thoroughly ("MAID gap"). Newly created ICD codes for MAID must include both disease-specific and symptom-oriented categories.

Conventional and assisted suicide in Switzerland: Insights into a divergent development based on cancer-associated self-initiated deaths.

BACKGROUND: We tested the hypothesis of supporters of assisted dying that assisted suicide (AS) might be able to prevent cases of conventional suicide (CS). METHODS: By using data from the Federal Statistical Office, we analyzed the long-term development of 30,756 self-initiated deaths in Switzerland over a 20-year period (1999-2018; CS: n = 22,018, AS: n = 8738), focusing on people suffering from cancer who died from AS or CS. RESULTS: While cancer was the most often listed principal disease for AS (n = 3580, 41.0% of AS cases), cancer was listed in only a small minority of CS cases (n = 832, 3.8% of CS cases). There was a significant increase in the absolute number of cancer-associated AS cases: comparing four 5-year periods, there was approximately a doubling of cases every 5 years (1999-2003: n = 228 vs.2004-2008: n = 474, +108% compared with the previous period; 2009-2013: n = 920, +94%; 2014-2018: n = 1958, +113%). The ratio of cancer-associated AS in relationship with all cancer-associated deaths increased over time to 2.3% in the last observation period (2014-2018). In parallel, the numbers of cancer-associated CS showed a downward trend only at the beginning of the observation period (1999-2003, n = 240 vs. 2004-2008, n = 199, -17%). Thereafter, the number of cases remained stable in the subsequent 5-year period (2009-2013, n = 187, -6%), and increased again toward the most recent period (2014-2018, n = 206, +10%). CONCLUSION: The assumption that, with the increasingly accessible option of AS for patients with cancer, CS suicide will become "superfluous" cannot be confirmed. There are strong reasons indicating that situations and circumstances of cancer-associated CS are different from those for cancer-associated AS.

Third International Consensus Conference on lesions of uncertain malignant potential in the breast (B3 lesions).

The heterogeneous group of B3 lesions in the breast harbors lesions with different malignant potential and progression risk. As several studies about B3 lesions have been published since the last Consensus in 2018, the 3rd International Consensus Conference discussed the six most relevant B3 lesions (atypical ductal hyperplasia (ADH), flat epithelial atypia (FEA), classical lobular neoplasia (LN), radial scar (RS), papillary lesions (PL) without atypia, and phyllodes tumors (PT)) and made recommendations for diagnostic and therapeutic approaches. Following a presentation of current data of each B3 lesion, the international and interdisciplinary panel of 33 specialists and key opinion leaders voted on the recommendations for further management after core-needle biopsy (CNB) and vacuum-assisted biopsy (VAB). In case of B3 lesion diagnosis on CNB, OE was recommended in ADH and PT, whereas in the other B3 lesions, vacuum-assisted excision was considered an equivalent alternative to OE. In ADH, most panelists (76%) recommended an open excision (OE) after diagnosis on VAB, whereas observation after a complete VAB-removal on imaging was accepted by 34%. In LN, the majority of the panel (90%) preferred observation following complete VAB-removal. Results were similar in RS (82%), PL (100%), and FEA (100%). In benign PT, a slim majority (55%) also recommended an observation after a complete VAB-removal. VAB with subsequent active surveillance can replace an open surgical intervention for most B3 lesions (RS, FEA, PL, PT, and LN). Compared to previous recommendations, there is an increasing trend to a de-escalating strategy in classical LN. Due to the higher risk of upgrade into malignancy, OE remains the preferred approach after the diagnosis of ADH.

The impact of intraoperative frozen section in patients with clinically node-negative breast cancer (cN0/ycN0) who received neoadjuvant systemic therapy.

BACKGROUND: When surgical axillary staging reveals residual metastatic deposits in breast cancer (BC) patients who had received neoadjuvant chemotherapy (NACT), axillary lymphonodectomy is indicated. In this study, we investigate whether it is reasonable to perform intraoperative frozen section (FS) of the removed sentinel lymph nodes (SLNs) in cases where NACT had been administered in patients who had a clinically negative nodal status at the time of diagnosis. PATIENTS AND METHODS: We analyzed data from 101 BCE patients with 103 carcinomas who were diagnosed between 2014 and 2021 and met the above-mentioned criteria. RESULTS: In three cases (2.8% of the study group), histologically active tumor tissue was detected in the removed axillary LNs. Discontinuation of therapy/the use of a low-dose NACT regimen was a significant factor for positive LNs (p = 0.02) at the subsequent surgical procedure; tumor progression during therapy approached borderline significance (p = 0.058). Among patients who had completed NACT with the planned standard dose regimen, and in which the primary tumors showed a response to therapy (n = 94), only one case had histologically detected residual metastases in the SLNs. CONCLUSIONS: Certified breast centers aim to improve the outcome of the patients. However, these specialized centers should also focus on economic aspects. This means that diagnostic and therapeutic procedures should be continuously critically reviewed in order to avoid unnecessary expenses. In BC patients with clinically node negative disease who completed NACT as planned and in which the tumor showed a good response to therapy, time consuming and costly FS of the SLNs removed should be omitted.

Long-term development of assisted suicide in Switzerland: analysis of a 20-year experience (1999-2018).

AIMS OF THE STUDY: The legalisation of assisted suicide is one of the most debated topics in the field of medical ethics worldwide. In countries in which assisted suicide is not legal, public discussions about its approval also encompass considerations of the long-term consequences that such legalisation would bring, for example, how many people will use this option, from what conditions would they be suffering, would there be differences between male and female assisted suicide and which developments and trends could be expected if there were to be a marked increase of cases of assisted suicide over time? METHODS: In order to answer these questions, we present the development of assisted suicide in Switzerland over a 20-year period (1999-2018; 8738 cases) using data from the Swiss Federal Statistical Office. RESULTS: During the observation period, the number of assisted suicides rose significantly: when four 5-year periods (1999-2003, 2004-2008, 2009-2013, 2014-2018) were analysed, the number of assisted suicide cases doubled over each period compared with the preceding one (Χ = 206.7, 270.4 and 897.4; p <0.001). The percentage of assisted suicides among all deaths rose from 0.2% (1999-2003; n = 582) to 1.5% (2014-2018: n = 4820). The majority of people who chose assisted suicide were elderly, with increasing age over time (median age in 1999-2003: 74.5 years vs 2014-2018: 80 years), and with a predominance of women (57.2% vs 42.8%). The most common underlying condition for assisted suicide was cancer (n = 3580, 41.0% of all assisted suicides). Over time, assisted suicide increased similarly for all underlying conditions; however, the proportion in each disease group remained unchanged. CONCLUSIONS: It is a matter of one's viewpoint whether the rise of assisted suicide cases should be considered alarming or not. These figures reflect an interesting social development but still do not appear to represent a mass phenomenon.

Factors Indicating Surgical Excision in Classical Type of Lobular Neoplasia of the Breast.

Purpose: Classical type of lobular neoplasia (LN) encompassing both atypical lobular hyperplasia and classical lobular carcinoma in situ of the breast is a lesion with uncertain malignant potential and has been the topic of several studies with conflicting outcome results. The aim of our study was to clarify outcome-relevant factors and treatment options of classical LN. Methods: We performed a pathological re-evaluation of the preoperative biopsy specimens and a retrospective clinical and radiological data analysis of 160 patients with LN from the Breast Center Zurich. Open surgery was performed in 65 patients, vacuum-assisted biopsy (VAB) in 79 patients, and surveillance after breast core needle biopsy (CNB) in 16 patients. Results: The upgrade rate into ductal carcinoma in situ/invasive cancer was the highest in case of imaging/histology discordance (40%). If the number of foci in the biopsy specimen was ≥3, the upgrade rate in the consecutive surgical specimens was increased (p = 0.01). The association of classical LN with histological microcalcification correlated with shortened disease-free survival (p < 0.01), whereas other factors showed no impact on follow-up. Conclusions: Surveillance or subsequent VAB after CNB of LN is sufficient in most cases. Careful consideration of individual radiological and histological factors is required to identify patients with a high risk of upgrade into malignancy. In those cases, surgical excision is indicated.

Biomarker dynamics and prognosis in breast cancer after neoadjuvant chemotherapy.

Breast cancer is a biologically diverse disease with treatment modalities selected based on tumor stage and tumor biology. Distinct intrinsic subtypes and surrogate biomarker profiles play a major role for therapeutic decisions. Response rates to systemic and local treatments as well as the interaction with epidemiological risk factors have been validated in clinical trials and translational studies. This retrospective study addresses the question how biomarker profiles and treatment modalities in the neoadjuvant chemotherapy setting have changed during the past 15 years and what prognostic impact these changes implicate. 342 female breast cancer stage I-IV patients receiving neoadjuvant chemotherapy between 2003 and 2017 were analyzed. Overall survival (OS) was correlated with preoperative clinical stage, postoperative pathological stage, treatment modalities and tumor biology before and after chemotherapy. Two subgroups were separated using an arbitrary cut-off year at 2009/2010, due to 2010 when platinum containing regimens were first administered. Median follow-up was 54 months. 57 (17%) patients died; recurrences occurred in 103 of 342 (30%) patients. Nodal stage and intrinsic subtypes (pre- and postoperative) significantly correlated with OS (p < 0.001). Preoperative histological grading lacked prognostic power. When comparing the patient characteristics of the subgroups, we found significant difference in the following characteristics: cT, ypT, ypN, pCR and chemotherapy regimens (p < 0.001). There was no difference in OS when comparing the two subgroups. Pathological complete response (pCR) rates had a significant impact on OS and disease-free survival (DFS) in HER2+ and triple negative subtypes (p = 0.03). In multivariate analysis, high proliferation index (> 30%), clinical metastatic stage and pathological tumor stage had prognostic impact on OS (p < 0.001, p = 0.0001, p = 0.002). Clinico-pathological factors and distinct therapy regiments especially in triple negative and HER2+ subtypes have prognostic impact on pCR, OS and DFS after neoadjuvant chemotherapy.

Diagnostic delay in moderately/poorly differentiated breast cancer types.

BACKGROUND: Diagnostic delay of breast cancer related to the false-negative assessment of the healthcare provider leads to tumor progression and might worsen the outcome. Previous studies found some factors associated with provider-related diagnostic delay; however, tumor biology has tended not to be considered. The aim of our study was to find differences in diagnostic delay of poorly differentiated breast cancer types. METHODS: Data of 970 patients with newly diagnosed moderately/poorly differentiated (G2/3) breast cancer at the age ≥40 years was retrospectively analyzed regarding breast cancer type, diagnostic delay and its consequence, clinical factors and physician's assessment. Multivariate analysis was used to evaluate associated factors with diagnostic delay. RESULTS: We observed a diagnostic delay in 3.8% (n = 37) of all patients. Mean delay time was 128 days, and clinically relevant tumor growth was observed in 43.2% of these cases. Delay was significantly higher in the group of triple-negative breast cancer (9.9% versus 2.7, 5.3 and 1.8% in hormonal receptor (HR)+/human epidermal growth factor receptor 2 (HER2)-, HR-/Her2+ and HR+/Her2+, respectively; P value <0.001). Age, breast density and reason for presentation were not correlated to diagnostic delay. CONCLUSION: Patients with triple-negative breast cancer are at higher risk of receiving a false-negative assessment and experiencing a diagnostic delay. Our results emphasize the importance of a detailed consideration of clinical risk factors and provider training and suggest a broad indication for a core needle biopsy.

Targeted Therapy in HR+ HER2- Metastatic Breast Cancer: Current Clinical Trials and Their Implications for CDK4/6 Inhibitor Therapy and beyond Treatment Options.

A metastatic state of breast cancer (MBC) affects hundreds of thousands of women worldwide. In hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) MBC, cyclin-dependent kinase (CDK)4/6 inhibitors can improve the progression-free survival (PFS), as well as the overall survival (OS), in selected patients and have been established as first- and second-line therapies. However, as MBC remains uncurable, resistance to CDK4/6 inhibitors occurs and requires alternative treatment approaches. Data on targeted therapy continue to mature, and the number of publications has been constantly rising. This review provides a summary and update on the clinical relevance, patient selection, ongoing trials of CDK4/6 inhibitors, and further targeted therapy options. It focuses on clinical aspects and practicability, as well as adverse events and patient-reported outcomes.

Breast Cancer Management During the COVID-19 Pandemic: The Senologic International Society Survey.

OBJECTIVE: In early 2020, the spread of coronavirus disease-2019 (COVID-19) led the World Health Organization to declare this disease a pandemic. Initial epidemiological data showed that patients with cancer were at high risk of developing severe forms of COVID-19. National scientific societies published recommendations modifying the patients' breast cancer (BC) management to preserve, in theory, quality oncologic care, avoiding the increased risk of contamination. The Senology International Society (SIS) decided to take an inventory of the actions taken worldwide. This study investigates COVID-19-related changes concerning BC management and analyzes the will to maintain them after the pandemic, evaluating their oncological safety consequences. MATERIALS AND METHODS: SIS network members participated in an online survey using a questionnaire (Microsoft® Forms) from June 15th to July 31st, 2020. RESULTS: Forty-five responses from 24 countries showed that screening programs had been suspended (68%); magnetic resonance imagines were postponed (73%); telemedicine was preferred when possible (71%). Surgeries were postponed: reconstructive (77%), for benign diseases (84%), and in patients with significant comorbidities (66%). Chemotherapy and radiotherapy protocols had been adapted in 28% of patients in both. Exception for telemedicine (34%), these changes in practice should not be continued. CONCLUSION: The SIS survey showed significant changes in BC's diagnosis and treatment during the first wave of the COVID-19 pandemic, but most of these changes should not be maintained. Indeed, women have fewer severe forms of COVID-19 and are less likely to die than men. The risk of dying from COVID-19 is more related to the presence of comorbidities and age than to BC. Stopping screening and delaying treatment leads to more advanced stages of BC. Only women aged over 65 with BC under treatment and comorbidities require adaptation of their cancer management.

Discrepancies between radiological and histological findings in preoperative core needle (CNB) and vacuum-assisted (VAB) breast biopsies.

BACKGROUND: Ultrasound (US)-guided breast biopsy is a routine diagnostic method used to correlate imaging finding to a histological diagnosis which is still the gold standard in preoperative diagnostics. The accuracy of US-guided breast biopsies relies on a precise radiologic-histopathologic correlation, which is discussed amongst an interdisciplinary team of gynecologists, radiologists and pathologists. However, false-negative or non-diagnostic biopsy results occur. Hence, a thorough and honest discussion to clarify the reason for discrepancies and to decide the next diagnostic step between specialists of the different disciplines is warranted. In this retrospective study, we analyzed discrepant findings between imaging and pathology results on preoperative breast biopsies. METHODS: Core and vacuum-assisted breast biopsies from 232 patients were included in this study. Inclusion criteria were (1) non-diagnostic (B1) category on histology independent from imaging category and (2) histological benign (B2) category with a BIRADS 5 (Breast Imaging Reporting and Data System) rating on imaging. Histological diagnoses were retrieved from all cases. Follow-up data were available in most cases. RESULTS: 138 biopsies were classified as B1, 94 biopsies as B2 category. 51 of 138 B1 cases (37%) underwent re-biopsy. Re-biopsy found malignancy (B5) in 19 of 51 cases, and B3/4 (premalignant) lesions in 3 of 51 cases. All B2 cases underwent second-look imaging-diagnosis, in 57 of 94 cases (66%) consecutive direct surgery or re-biopsy. Of these, malignancy was diagnosed histologically in 26 of 57 cases (45.6%). CONCLUSION: Determining imaging-pathology concordance after US-guided breast biopsy is essential. Discrepant cases and further diagnostic steps need to be discussed with an interdisciplinary approach.

Metastatic Breast Cancer as a Chronic Disease: Evidence-Based Data on a Theoretical Concept.

BACKGROUND: We challenge the concept of metastatic breast cancer (MBC) as a chronic disease. METHODS: We analyzed an unselected cohort of 367 patients who were diagnosed with MBC over a 22-year period (1990-2011). RESULTS: In order to create a "chronic disease subgroup", we separated those patients from the entire cohort in whom systemic therapy was not applied after the diagnosis of MBC (n = 53; 14.4%). Three hundred fourteen patients (85.6%) comprised the "chronic disease subgroup". The vast majority of those patients (89.8%) died of progressive disease after a median metastatic disease survival (MDS) of 25 months. Twenty patients (6.4%) died of non-MBC-related causes (MDS 38.5 months). Approximately 1 in 4 patients (26.8%) died within the first year after the MBC diagnosis. The 3- and 5-year MDS rates were 35.4 and 16.2%, respectively. Only 12 patients (3.8%) were exceptional survivors (MDS >10 years). CONCLUSION: The term "chronic disease" might be appropriate in selected MBC cases, bringing MBC into alignment with "classical" chronic diseases such as diabetes and hypertension. However, most cases display fundamental differences with regard to temporal progression and above all the case fatality rate. More than 90% of patients in the "chronic disease subgroup" died of the disease with a MDS of 2-3 years (even those who underwent systemic palliative therapies). Doctors and patients might understand the term "chronic disease" differently. The term must be used sparingly and explained carefully in order to create a common level of communication based on a shared understanding which avoids awakening false hopes and fostering misleading expectations.

Differential prognostic value of positive HER2 status determined by immunohistochemistry or fluorescence in situ hybridization in breast cancer.

PURPOSE: Human epidermal growth factor-receptor-2 (HER2) is a membrane-tyrosine-kinase that is amplified/overexpressed up to 20% in breast cancer. HER2 positive status is associated with faster disease progression, higher metastatic potential, and shorter disease-free/overall survival and also has emerged as an important therapeutic target in breast cancer. HER2 status can be determined by in-situ-hybridization (ISH) or immunohistochemistry (IHC). Although the concordance rate between ISH and IHC is well-known, the prognostic power of both technologies if tested in parallel on the same tumor has not been studied extensively. METHODS: In this study we retrospectively analyzed a large HER2 positive breast cancer cohort tested both with fluorescence labeled ISH (FISH) and IHC in parallel on each case. We stratified HER2 positive results by FISH and IHC with long-term overall survival, 5-year survival and metastases/recurrence rates. Positive HER2 status both FISH and IHC was available in 364 patients. RESULTS: The number of HER2 FISH-positive and FISH-negative patients was 342 and 22, respectively. The number of HER2 IHC 0/1 + , IHC 2 + , and IHC 3 + patients was 12, 42, and 310, respectively. Among the patients with IHC 3 + status, 288 were FISH-positive and 22 FISH-negative. HER2 status determined by FISH correlated with clinical outcomes (overall survival and with metastases/recurrence, p = 0.036, p = 0.039), whereas HER2 status determined by IHC did not. CONCLUSION: Our results indicate that prognostic information in HER2 positive breast cancer also depends on the methodology of how positivity was determined. In our cohort, FISH was superior to IHC based positive HER2 status.

Breast-conserving surgery with intraoperative radiotherapy in recurrent breast cancer: the patient's perspective.

PURPOSE: When ipsilateral breast-tumor recurrence (IBTR) following breast-conserving surgery (BCS) occurs, the cure of a potentially life-threatening disease is the main goal. If, however, this is diagnosed early, prognosis is still good and patient-reported outcomes become more important. Despite the fact that many patients would prefer a further BCS, international breast cancer guidelines still recommend mastectomy, mainly because previous radiation implies limited options. Our comparative study evaluates the long-term quality-of-life and outcome in patients with IBTR who received BCS plus intraoperative radiotherapy (IORT) versus mastectomy. METHODS: Patients with IBTR were retrospectively divided into three groups according to the local treatment: group 1 (n = 26) was treated with BCS + IORT; group 2 (n = 35) received a standard mastectomy; group 3 (n = 52) had a mastectomy with subsequent reconstruction. Outcomes were analyzed after a mean follow-up of 5 years after IBTR. Quality-of-life was evaluated by the validated questionnaire BREAST-Q in 50 patients who fulfilled the inclusion criteria. RESULTS: Quality-of-life scores varied within the groups, ranging from 51.4 to 91.3 (out of 100 points). We observed satisfactory scores in all items, with no statistical difference within the groups. Disease-free survival of all groups did not statistically differ, and overall mortality was very low (0.9%). The postinterventional complication rate was lower after BCS (19.2% versus 34.3% after mastectomy and 30.8% after mastectomy with reconstruction). CONCLUSION: For patients with previous surgery and radiation who demand a second BCS in the recurrent situation, this surgical technique can be offered in combination with IORT. Our long-term results imply oncological safety, lower complication rate, and good patient satisfaction.

Clinical Imaging of the Heterogeneous Group of Triple-negative Breast Cancer.

BACKGROUND/AIM: Triple-negative breast cancer (TNBC) can be divided into subtypes of basal-like (BL), mesenchymal-like (ML), luminal androgen receptor (LAR), and immunomodulatory (IM). The aim of our study was to assess whether there are distinct radiologic features within the different TNBC subtypes and whether this has potential clinical impact. PATIENTS AND METHODS: Imaging pictures of 135 patients with TNBC were re-evaluated. TNBC subtyping was performed on asservated tumor tissue using a panel of antibodies. RESULTS: Mammographic margins of LAR-TNBC were more often spiculated (24.3% versus 0-4.1%). BL-TNBC presented more frequent a mass without calcification in mammogram than other subtypes (71.4% versus 48.6-57.9%). In ultrasound, ML and LAR were described more often with smooth borders. CONCLUSION: The histopathological subtype of TNBC influences its presentation in ultrasound and mammogram. This can reflect a different growth pattern of the subtypes and may have an impact on the early diagnosis of TNBC.

Radiological Staging for Distant Metastases in Breast Cancer Patients with Confirmed Local and/or Locoregional Recurrence: How Useful are Current Guideline Recommendations?

BACKGROUND: Breast cancer patients with local and/or locoregional recurrence (LR) are at higher risk of developing distant metastases (DM) at a later time. Once LR has been confirmed, some international interdisciplinary guidelines recommend performing radiological examinations for DM to determine the course of further therapy (curative or palliative approach). This study analyzed the metastatic patterns of patients with LR with particular regard to the frequency of concurrent diagnosis of LR and DM; in other words: are radiological staging procedures actually justified for DM at the time of diagnosis of LR? METHODS: This study included all patients (n = 1368) who were diagnosed and treated for nonmetastatic breast cancer (Stage I-III) at the University Women's Hospital Basel, Switzerland between 1990 and 2009. RESULTS: In 137 patients, LR was diagnosed without a history of DM: in-breast/thoracic wall only, n = 90 (65.7%); involvement of axillary/supra-/infraclavicular lymph nodes, n = 47 (34.3%). DM was found at the time of diagnosis of LR in 44 patients (32.1%). Concurrent diagnosis of LR and DM occurred significantly more often in patients with lymph node recurrence compared with those with in-breast/chest wall recurrence (48.9% vs. 23.3%; p = 0.004). CONCLUSIONS: Approximately one-third of patients with a LR had synchronous DM at the time of their local/locoregional event. For this reason, routine systemic staging imaging at the time of LR should be an absolute requirement for planning further therapy. Confirmation of DM may spare the patients radical surgical interventions with questionable impact on survival in the face of an incurable disease.

Long-Term Survival and Cure in Distant Metastatic Breast Cancer.

BACKGROUND: Previous data showed that distant metastatic breast cancer (MBC) might be curable in up to 3% of the cases in selected patients, mostly young, with good performance status and with low-volume metastatic disease, mainly by an aggressive multidisciplinary approach including aggressive combination chemotherapy regimens. These long-lasting responses question the belief that MBC is wholly incurable. This study evaluates the rate of long-term survivors and potentially cured patients in an unselected cohort of MBC patients. METHODS: We analyzed the data from 342 patients in whom distant MBC was diagnosed from 1990 to 2011. For this study, we defined a metastatic disease survival (MDS) of 9 years as inclusion criterion for long-term survivorship. RESULTS: Eighteen patients (5.3%) were long-term survivors (MDS: 126 months; range, 108-300 months). The rate of long-term survivors was equally distributed over time (1990-1999: 4.3% vs. 2000-2011: 5.9%, p = 0.63). Compared to patients who had a lower MDS, long-term survivors had significantly more often primary MBC (p = 0.005) and hormone receptor-positive carcinomas (p = 0.015). Age at MBC diagnosis, presence of visceral metastases, and limited number of metastatic sites at the time of MBC diagnosis appeared to have no significant impact on long-term survival. Long-term survival was not associated with the use of chemotherapy (50.0% vs. 65.7% in the control group, p = 0.21). Eight patients (2.3%) developed a complete remission and presented with no evidence of disease at the time of last follow-up (MDS: 234.5 months). CONCLUSION: Since long-term survivors in MBC comprise a relatively heterogeneous group, the factors that lead to the quite rare and felicitous case of long-term survival or even cure can hardly be evaluated systematically. Some patients may be considered cured of their disease. This fraction may be small, but the chance of survival, and even of cure, truly exists. Perhaps we must accept that the factors contributing to long-term survival remain an enigma. It appears, however, that aggressive chemotherapy is not the only key factor to long-term remission.

Noncompliance with palliative systemic therapy in patients with distant metastatic breast cancer: a blind spot for oncologists?

PURPOSE: The goal of our study was to provide a general overview of noncompliance with palliative systemic therapy in distant metastatic breast cancer (MBC). METHODS: We analyzed an unselected cohort of 339 patients who were diagnosed with MBC over a 22-year period (1990-2011, age restriction: ≥ 85 years old). RESULTS: Forty patients (11.8%) rejected the offered or recommended systemic therapy (age distribution of this noncompliance subgroup: ≤60 years at MBC diagnosis: 7.9%; 60-70 years: 13.2%; > 70 years: 15.6%). The rate of noncompliance was equally distributed over time (1990-1999: 12.2% vs. 2000-2011: 11.5%, p = 0.87). Compared to patients who had received palliative antineoplastic systemic therapy, those who remained untreated were significantly older (70 vs. 61 years, p = 0.015), had shorter metastatic disease survival (2 vs. 27 months, p < 0.001), had more often an aggressive tumor subtype (hormone-receptor negative carcinomas: 48.7% vs. 22.2%, p < 0.001), and had more often secondary MBC (95.0% vs. 73.6%, p = 0.001). CONCLUSIONS: Although the high rate of noncompliance in the subgroup of elderly patients was not unexpected, it is noticeable that even in the subgroup of patients who were younger than 60 years, approximately 8% also rejected any systemic therapy before a MBC-related death occurred This group of younger women rarely had any relevant comorbidities, were potential candidates for chemotherapy and knowingly declined the therapy options. Such patients are never or seldom seen by oncologists in their daily practice and therefore play a minor role in their personal perception of disease. Nevertheless, these under-reported cases make up a significant proportion of MBC.

Prospective Evaluation of Residual Breast Tissue After Skin- or Nipple-Sparing Mastectomy: Results of the SKINI-Trial.

OBJECTIVE: This study was designed to investigate the presence of residual breast tissue (RBT) after skin-sparing mastectomy (SSM) and nipple-sparing mastectomy (NSM) and to analyse patient- and therapy-related factors associated with RBT. Skin-sparing mastectomy and NSM are increasingly used surgical procedures. Prospective data on the completeness of breast tissue resection is lacking. However, such data are crucial for assessing oncologic safety of risk-reducing and curative mastectomies. METHODS: Between April 2016 and August 2017, 99 SSM and 61 NSM were performed according to the SKINI-trial protocol, under either curative (n = 109) or risk-reducing (n = 51) indication. After breast removal, biopsies from the skin envelope (10 biopsies per SSM, 14 biopsies per NSM) were taken in predefined radial localizations and assessed histologically for the presence of RBT and of residual disease. RESULTS: Residual breast tissue was detected in 82 (51.3%) mastectomies. The median RBT percentage per breast was 7.1%. Of all factors considered, only type of surgery (40.4% for SSM vs. 68.9% for NSM; P < 0.001) and surgeon (P < 0.001) were significantly associated with RBT. None of the remaining factors, e.g., skin flap necrosis, was associated significantly with RBT. Residual disease was detected in three biopsies. CONCLUSIONS: Residual breast tissue is commonly observed after SSM and NSM. In contrast, invasive or in situ carcinomas are rarely found in the skin envelope. Radicality of mastectomy in this trial is not associated with increased incidence of skin flap necrosis. ClinicalTrials.gov Identifier NCT03470909.